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Salvianolic acid B suppresses maturation of human monocyte‐derived dendritic cells by activating PPARγ
Author(s) -
Sun Aijun,
Liu Hongying,
Wang Shijun,
Shi Dazhuo,
Xu Lei,
Cheng Yong,
Wang Keqiang,
Chen Keji,
Zou Yunzeng,
Ge Junbo
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01518.x
Subject(s) - cd86 , tlr4 , chemistry , cd40 , p38 mitogen activated protein kinases , mapk/erk pathway , monocyte , peroxisome proliferator activated receptor , microbiology and biotechnology , receptor , signal transduction , biochemistry , biology , in vitro , immunology , cytotoxic t cell , gene , phenotype
BACKGROUND AND PURPOSE Salvianolic acid B (Sal B), a water‐soluble antioxidant derived from a Chinese medicinal herb, is known to be effective in the prevention of atherosclerosis. Here, we tested the hypothesis that the anti‐atherosclerotic effect of Sal B might be mediated by suppressing maturation of human monocyte‐derived dendritic cells (h‐monDC). EXPERIMENTAL APPROACH h‐monDC were derived by incubating purified human monocytes with GM‐CSF and IL‐4. h‐monDC were pre‐incubated with or without Sal B and stimulated by oxidized low‐density lipoprotein (ox‐LDL) in the presence or absence of PPARγ siRNA. Expression of h‐monDC membrane molecules (CD40, CD86, CD1a, HLA‐DR) were analysed by FACS, cytokines were measured by elisa and the TLR4‐associated signalling pathway was determined by Western blotting. KEY RESULTS Ox‐LDL promoted h‐monDC maturation, stimulated CD40, CD86, CD1a, HLA‐DR expression and IL‐12, IL‐10, TNF‐α production; and up‐regulated TLR4 signalling. These effects were inhibited by Sal B. Sal B also triggered PPARγ activation and promoted PPARγ nuclear translocation, attenuated ox‐LDL‐induced up‐regulation of TLR4 and myeloid differentiation primary‐response protein 88 and inhibited the downstream p38‐MAPK signalling cascade. Knocking down PPARγ with the corresponding siRNA blocked these effects of Sal B. CONCLUSIONS AND IMPLICATIONS Our data suggested that Sal B effectively suppressed maturation of h‐monDC induced by ox‐LDL through PPARγ activation.